poly(meth)acrylates obtained by cascade reaction

Feature Article

Poly(meth)acrylates Obtained by CascadeReaction

Dragos Popescu, Helmut Keul,* Martin Moeller*

Preparation, purification, and stabilization of functional (meth)acrylates with a high dipolemoment are complex, laborious, and expensive processes. In order to avoid purification andstabilization of the highly reactive functional monomers, a concept of cascade reactions wasdeveloped comprising enzymatic monomer synthesis and radical polymerization. Transacylationofmethyl acrylate (MA) andmethylmethacrylate (MMA)with different functional alcohols, diols,and triols (1,2,6-hexanetriol and glycerol) in the presence ofNovozyme 435 led to functional (meth)acrylates. After theremoval of the enzyme by means of filtration, removal ofexcess (meth)acrylate and/or addition of a new monomer,e.g., 2-hydroxyethyl (meth)acrylate the (co)polymerizationvia free radical (FRP) or nitroxide mediated radicalpolymerization (NMP) resulted in poly[(meth)acrylate]swith predefined functionalities. Hydrophilic, hydrophobicas well as ionic repeating units were assembled within thecopolymer. The transacylation of MA and MMA with diolsand triols carried out under mild conditions is an easy andrapid process and is suitable for the preparation of sensitivemonomers.

Introduction

Polymeric materials are indispensable in modern society.

They are widely used as commodity materials in everyday’s

life and as highly advanced materials in electronics,

machinery, communication, transportation, pharmacy,

medicine, etc. Today, a society without polymeric materials

is hard to imagine.

Polymers which are prepared fully or partially from

acrylates or methacrylates are called poly(meth)acrylates.

Numerous fields of application of poly(meth)acrylates

are known, such as fiber protection agents in laundry

H. Keul, M. Moeller, D. PopescuInstitute of Technical and Macromolecular Chemistry, RWTHAachen and DWI an der RWTH Aachen e.V., Pauwelsstr. 8,D-52056 Aachen, GermanyE-mail: [email protected]; [email protected]

Macromol. Rapid Commun. 2011, 32, 559–572

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detergents, corrosion protection, or as complexing agents.

The end use of poly(meth)acrylates depends on the

monomer composition or the modification of the polymers

after their synthesis. Polymers with pendant functional

groups have gained much attention in the last few years[1]

and are of interest as starting materials for complex

polymer architectures or for polymers with customized

properties for different applications.[2]

The development of new polymeric materials is closely

linked to the polymerization procedures. Radical polymer-

ization is a widely used technique in industry for the

preparation of polymers, like poly(styrene) and poly(-

methyl methacrylate). Although radical chain reactions are

known since the twenties of the last century, it was not

until the mid 1950 s that the free-radical polymerization

was introduced into technical applications. Nowadays,

free-radical polymerization is used for the synthesis of

many important classes of polymers such as polymetha-

elibrary.com DOI: 10.1002/marc.201000725 559

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D. Popescu, H. Keul, M. Moeller

crylates, polystyrene, polychloroprene, polyacrylonitrile,

polyethylene, and a large number of copolymers. Many

reviews on this subject are available.[3–5] The major

advantage of radical polymerization is that it is carried

out under relatively undemanding conditions: water or

other impurities are well tolerated; the reactions occur in a

broad temperature range from 0 to 100 8C;[6] high molecular

weight polymers are obtained without removal of stabi-

lizers present in commercial monomers and are also

produced in the presence of trace amounts of oxygen. It

is for these reasons that radical polymerization has been

adopted for many industrial polymer syntheses.

The major drawbacks of conventional radical polymer-

izations are related to the lack of control over the polymer

microstructure which is particularly important for the

preparation of more complex polymer structures such as

block copolymers or gradient copolymers. The design of

complex macromolecular architectures has become a

particular focus in polymer science. Some of these

architectures possess unique properties, which make them

interesting candidates for specialty applications in nanos-

tructured and biomedical materials. Such precise macro-

molecular syntheses employ concepts of ‘‘living’’ polymer-

ization. The concept of living polymerization was

introduced by Szwarc for the anionic polymerization of

Helmut Keul studied chemistry at the University of TeUniversity of Karlsruhe, Germany. Post-doctoral workUniversity ofMichigan (Ann Arbor), USA, was followedAachen in 1986. His current interests regard the controstructure-property relationships. At the timeDr. Keul isTechnical Chemistry and Macromolecular Chemistry (IT200 scientific publications and 20 patents.

Martin Moller was born in 1951. He received his Ph.D.Lynen-Research Fellow of the Alexander von Humboldtof Massachusetts, Amherst (USA), he returned to Freilecturer on Macromolecular Chemistry from the UniDepartment of Chemical Technology, University of TwUlm and Head of the Department of Organic ChemistrTextile Chemistry and Macromolecular Chemistry of RWinstitute DWI. He ismember of Deutsche Akademie derthe State of North-RhineWestphalia. In 2003, he was awas elected scientific expert of Deutsche Forschungsgfur Angelegenheiten der Sonderforschungsbereiche’ oscientific journals. He has published about 450 articlefunctional nanostructures, synthesis and structure pblockcopolymers, surface modification, self organizati

Dragos Popescuwas born in 1980 in Bucharest (Romanhe received the M.Sc. degree in therapeutical chemistresearch scholarship at DWI an der RWTHAachen e.V. (Gobtained the Ph.D. degree under the supervision of ProChemistry, RWTH Aachen and DWI an der RWTH Aachmultifunctional and reactive poly(meth)acrylates. SinComposite Resins in the Chemistry and Synthesis gro

Macromol. Rapid Commun

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styrene,[7,8] later the concept was transferred to cationic

vinyl polymerization[9,10] and to ionic (anionic and cationic)

ring opening polymerizations (ROPs).[11–14] Much later, at

the end of 20th century, controlled radical polymerization

(CRP) was introduced: atom transfer radical polymerization

(ATRP),[15–20] nitroxide mediated radical polymerization

(NMP),[21,22] and reversible addition fragmentation chain

transfer polymerization (RAFT).[23,24] All these CRP methods

are based on a fast equilibrium between dormant and active

species. The equilibrium constants are low, keeping the

concentration of the active species very low (ca. 10�7

mol � L�1). As a result, termination and transfer reactions are

minimized, and CRP can be achieved under appropriate

polymerization conditions.

Although the CRP processes—ATRP, NMP, and RAFT—

were developed within the last decade, these techniques

already find applications in the commercial production of

new materials.[25] Block copolymers based on acrylates find

applications as thermoplastic elastomers,[26] adhesives,

lubricants, gels, and coatings. However, they can also be

used for more sophisticated applications such as specialized

chromatographic packing[27] or controlled drug-delivery in

cardiovascular stents.[28]

The CRP techniques allow the straightforward synthesis

of well-defined polymers and copolymers with desired

chnology, Bucharest, Romania, and received his PhD in 1973 at theat the University of Karlsruhe and visiting research scientist at thebymoves to the University of Bayreuth in 1984 and the University oflled synthesis of multifunctional and reactive polymers as well asleading a research group of fifteen Ph.D. students at the Institute ofMC) of the RWTH Aachen University. He is an author of more than

from the University of Freiburg in 1981. After working as a Feodor-Foundation at the Department of Polymer Science of the Universityburg in 1982. In 1988, he received his qualification as a universityversity of Freiburg. From 1989 till 1993, he was professor at theente (NL). From 1993 to 2002, he was professor at the University ofy III / Macromolecular Chemistry. In 2002, he became professor forTH Aachen University and since 2003, he is also the director of theTechnikwissenschaften (acatech) and of the Academy of Sciences ofwarded the Korber European Science Award. From 1999 to 2005, heemeinschaft (DFG). Since 2006, he is member of ‘Senatsausschussf the DFG. He is member of the editorial board of several polymers. His main research interests are macromolecular chemistry androperty relationships in branched and hyper-branched polymers,on of polymers in the bulk and in thin films.

ia). In 2003 he obtained his B.Sc. degree in biochemistry and in 2005ry at the University of Bucharest (Romania). After a three monthermany), he started in October 2005with his Ph.D. work. In 2010 hefessor Martin Moller at Institute of Technical and Macromolecularen e.V. His research focused on the chemoenzymatic synthesis ofce August 2010 he is working as a project coordinator for DSMup.

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Poly(meth)acrylates Obtained by Cascade Reaction

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molecular weight, molecular weight distribution, composi-

tion and microstructure, architecture and functionality.

These parameters strongly influence the response to

external stimuli as for example temperature in stimuli-

responsive polymers.[29] Depending on the structure,

polymers exhibit a phase transition from soluble to

insoluble upon heating in aqueous solution. Such polymers

show a lower critical solution temperature (LCST) which is

based on the existence of hydrogen bonding between the

solvent molecules and the polymer chain. Thus, in aqueous

solutions, below the LCST, the polymer chains are soluble

and exist in a random coil conformation. Weakening of

the hydrogen bonds at higher temperatures causes entropy-

driven phase transition of the polymer to a hydrophobic

collapsed state.[30] Polymers with an LCST show a sudden

and mostly reversible change from hydrophilic to hydro-

phobic that makes them attractive for switchable materials

in biotechnological applications including drug delivery

systems,[31] tissue engineering,[32] and biomolecule separa-

tion[33,34] but are also of interest for industrial applications

in catalysis,[35] coatings, and even in textile materials.

Synthesis of Functional Polyacrylates

The target of macromolecular engineering is to design and

to control the structural parameters of multifunctional

polymers such as chain length, polydispersity, functional

composition, and microstructure, in order to adjust their

macroscopic properties.[36] Homo- and copolymers with

functional groups as lateral substituents are of increasing

interest in polymer science. Several strategies were

developed for the preparation of functional polymers such

as (i) (co)polymerization of functional monomers and

(ii) polymer analogous reactions using polymers with

reactive groups. Polymerization of functional monomers to

yield functional polymers sometimes is not the method of

choice due to the difficulty of both the preparation of the

monomers and their polymerization.[37] The second con-

cept for the preparation of functional polymers consists of

the modification of the pending groups of a polymer.

Acrylates are an important class of monomers for

technical applications that are found in a variety of

consumer products. Based on their reactivity and function-

ality they are used for the preparation of polymers of

different architecture and resins for surface coatings.

Acrylate chemistry is by far the most commonly used

technology in UV-cured coatings. It involves the introduc-

tion of cross-linking functionalities in the form of acrylate

groups to create binders for the use in surface formulations.

Hydroxy functional acrylates and methacrylates are

interesting precursors for hydrophilic and water-soluble

polymers which are promising functional polymers for

biotechnological applications,[38,39] including biomedical

and pharmaceutical products such as contact lenses, dental

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materials, encapsulated cells, carriers for controlled drug

delivery as well as hydrogels.[31,40,41] Hydroxy functional

acrylates and methacrylates are versatile and ideal co-

monomers for cross-linking via the pendant hydroxy group;

they can be used as precursors for further chemical

modification leading to novel building blocks.

For the preparation of functional acrylates or methacry-

lates the chemical synthesis is based for example on the

reaction of acrylic and methacrylic acid with cyclic ethers

like ethylene oxide and propylene oxide.[42] When cyclic

ethers are not available or not reactive enough, the reaction

of rather expensive acid chlorides or active esters of

(meth)acrylic acids[43–45] with alcohols or amines is the

method of choice. Chemical synthesis with nonactivated

(meth)acrylic alkyl esters requires high temperatures,

pressure, acidic catalysts, polymerization inhibitors, and

complex purification procedures to isolate the mono-

(meth)acrylates from the mixture of mono- and multi-

functional monomers, leading to low overall yields. In the

case of base-catalyzed transesterification the products are

often complex mixtures, occasionally colored. In order to

remove the coloration and the unconverted reactants it is

necessary to work up the product mixtures by means of

costly and inconvenient washing procedures or by distilla-

tion. However, the monomers often are not stable under

distillation conditions and polymerization may occur.

Further development of syntheses of functional acrylates

and methacrylates as well as of multifunctional poly-

(meth)acrylates is an area of major interest because of their

high performance potential.

Enzyme Catalyzed Transacylation

An alternative to conventional chemical syntheses for the

production of fine chemicals is the enzyme catalyzed

transformation. In contrast to ‘‘chemical’’ metal catalysts,

which might be toxic, enzymes are natural (‘‘green’’)

biocatalysts. In their natural environment enzymes

are efficient catalysts and show high chemoselectivity,

regioselectivity, and enantioselectivity. More than

hundred years ago, it was shown that enzymes can be

used in organic solvents.[46]. Their high selectivity and

activity in organic solvents make them ideal catalysts for

chemical conversions. In vivo, enzymatic catalyses obey

two fundamental characteristics: the first is the ‘‘key and

lock’’ principle proposed by Emil Fischer in 1894 which

points out the relationship between an enzyme and a

substrate and the second suggested by Linus Pauling

explaining the decrease of the activation energy by the

formation of an enzyme-substrate complex (transition-

state). However, the interest for biocatalysis did not boost

until the 1980 s with the general acceptance that enzymes

can catalyze unnatural reactions efficiently in organic

solvents.[47]

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In recent years, the employment of triacylglycerol lipases

as biocatalysts for transacylation reactions (transesterifica-

tion) has emerged as a potential route to replace conven-

tional chemical methods. The main reason for this is the

hope for more efficient processes with higher chemo-, regio-,

and stereoselectivity. In addition, the use of lipases as

catalysts is a non-toxic and environmentally friendly

technology and requires mild operating conditions com-

pared to many chemical procedures.[48,49] Besides, the

availability of lipases from different microbial sources

possessing specificity of action and the fact that their

catalytic activity can be easily regulated are some of the

highlights that most chemical catalysts do not possess. So

far, the most widely used enzyme for esterification and

transacylation reactions is lipase B fromCandidaantarctica

(CALB), immobilized by adsorption on a macroporous

acrylic resins, [Lewatit VP OC 1600, Bayer, poly(methyl

methacrylate-co-divinylbenzene)] called Novozyme 435,

which has exceptionally high activity and versatility.[50–53]

The yeast C. antarctica was originally isolated in Antarctica

and was found to produce two lipase variants (CALA and

CALB).[54] CALB belongs to the a/b-hydrolase-fold super-

family which contains enzymes that evolved from a

Asp

O

O

NNH

His

H,CH3

O

OCH3

H O

Ser

Asp

O

O

NNH

His

H O

Ser

O OR

H,CH3

k-4k4 H,CH3

Figure 1. Ping-pong mechanism of the transacylation reaction cataly



common ancestor and is built up by 317 amino acids

having a molecular weight of 33 kDa.[55] The active site of

CALB is illustrated in Figure 1. It contains the catalytic triad

Ser105-His224-Asp187, common to all serine hydrolases.

CALB catalyses acyl-transfer reactions and follows the

ping-pong mechanism comprising four steps: (i) the first

substrate enters the active site and the first tetrahedral

intermediate is formed; (ii) the first product leaves the

active site and the acyl-enzyme is formed; (iii) the second

substrate enters the active site and the second tetrahedral

intermediate is formed; (iv) the second product leaves the

active site and the enzyme is ready for another catalytic

cycle.

Numerous reports have appeared in the literature on the

lipase-catalyzed ester synthesis, with monoalcohols[57–59]

as well as diols and triols demonstrating the regioselective

acylation of primary alcohols in organic solvents.[60–62]

Moreover, the use of acrylic and methacrylic esters in

transacylation reaction using lipases was investigated

earlier.

Ghogare and Kumar reported the lipase-catalyzed

acrylation of various alcohols including 2-ethylhexane-

1,3-diol with an activated 2,3-butanedione monooxime

Asp

O

O

NNH

His

k1k-1

H O

Ser

O OH3C

H,CH3

Asp

O

O

NNH

His

Ser

OO

H,CH3

H3C OHHO R

k2k-2

k-3k3

O

OR

zed by CALB.[56]

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acrylate,[63] while enzymatic transacylation of vinyl

acrylate with alcohols using immobilized lipase from

C. cylindracea was reported by Ikeda et al.[64] A frequent

disadvantage of these reactions is the need to use activated

acrylates, such as the oximes or vinyl esters, which are

expensive and difficult to obtain. Hajjar et al. described

the enzymatic transacylation of cyclic and open-chain

alkane diols with ethyl acrylate using a lipase from

Chromobacterium viscosum. The reaction proceeds with

an excess of alkyl acrylate with respect to the diol in a

system without solvent producing a mixture of mono- and

bisacrylates.[65]

A highly stabilized, immobilized pig liver esterase was

found to be effective in catalyzing both hydrolysis and

transesterification reactions of methyl and ethyl esters of

acrylic and methacrylic acids. The enzyme was successfully

employed for the preparation of hydroxy and dihydroxy

alkyl acrylates and methacrylates without formation of bis-

or tris(meth)acrylates by using an alcohol excess of 50–70%

v/v.[66] The lipase PS-30 Pseudomonas species-catalyzed

preparation of carbamoyloxyethyl methacrylate by trans-

acylation of 2-hydroxyethyl carbamate with vinyl metha-

crylate in a solvent mixture of toluene/THF (3:1) was

reported by Derango et al.[67] Complete conversion is

achieved with the specific vinyl methacrylate reactant,

since vinyl alcohol liberated is removed from the reaction

equilibrium in the form of acetaldehyde.

In another study, Warwel et al. used Novozyme 435 as

biocatalyst for the transacylation of methyl acrylate (MA)

and methyl methacrylate (MMA) with unsaturated fatty

alcohols,[68] while Athawale et al. performed a comprehen-

sive study of the reaction parameters governing the

enzymatic synthesis of geranyl methacrylate using porcine

pancreatic lipase and 2,3-butanedione mono-oxime metha-

crylate as acyl donor in diisopropyl ether as the solvent.[69] A

comparative study of the enzymatic synthesis of acrylic

acid esters of different alcohols using 2,3-butanedione

mono-oxime acrylate and vinyl acrylate as acylating agents

and the immobilized lipase from C. cylindracea (CCL) was

reported.[70] The rate of conversion was fastest when the

oxime acrylate was used. Effect of solvents on the rate of

conversion was studied and diisopropyl ether was proved

to be a better solvent than CHCl3 and THF. Various alcohols

were used to study the effect of the structure of the alcohol

on the rate of conversion. Among the linear alcohols

studied, ease of conversion was found to be of the order

n-octanol>n-hexanol>n-butanol. In the case of cyclo-

hexyl methanol, highest conversion (80%) was achieved.

Epoxy-containing (meth)acrylic esters can also be

obtained by lipase-catalyzed reaction. Thus, Xin et al.

described for the first time the synthesis of glycidyl acrylate

from glycidol and vinyl acrylate studying the influence of

three different lipases, four solvents, and polymeric

additives on the conversion.[71] Quantitative conversions




were not obtained since all the reactions were terminated at

a maximum conversion of 75% after 4 h. However, due to

their high preparation costs, such acrylic acid derivates are

not of technical interest.

This drawback was overcome by one of the BASF patents

where epoxy-containing (meth)acrylic esters were

obtained by transacylation of (meth)acrylic esters available

on industrial scale and alcohols comprising epoxy groups in

the presence of lipase B from C. antarctica.[72] Numerous

other patents on the lipase catalyzed transacylation have

appeared in the literature showing the industrial relevance

of this research.[73–78]

Chemoenzymatic Approach toward PolymericMaterials

An exhaustive study on combining chemical and enzyma-

tical steps was performed by the groups of Palmans and

Heise in Eindhoven.[79] Thus, the first combination of an

enzymatic polymerization with a chemical polymerization

technique: lipase-catalyzed ROP of e-caprolactone and ATRP

of styrene was reported.[80,81] This approach was extended

by using methyl-substituted e-caprolactones as a substrate

for the enzymatical step and MMA for ATRP.[82] A novel

chemoenzymatic approach toward polymeric materials

by integration of enzymatic ROP with nitroxide mediated

polymerization was described as well.[83] Peeters et al.

reported for the first time the synthesis of branched

polymers following the alternative strategy of self con-

densing vinyl polymerization (SCVP) of fully enzymatically

generated macroinimers by radical polymerization.[84] Yu

and Lowe reported the enzymatic reaction between an

amino alcohol and vinyl methacrylate followed by RAFT

polymerization of the newly synthesized monomer.[85] The

Institute of Technical and Macromolecular Chemistry,

RWTH Aachen, for the first time reported that chloroper-

oxidase (CPO) is stable in scCO2/H2O biphasic media. This

allows the cascading of chemical and enzymatic reactions

for the synthesis of optically enriched (R)-sulfoxide.[86]

The chemo-enzymatic methodology opens new oppor-

tunities for the efficient integration of enzymes and

chemical catalysts toward cascade reactions. A broad

literature presents the chemo-enzymatic synthesis of

polyacrylates containing sucrose functionalities based on

the cascade reaction methodology.[87–92]

This paper will point out the features and the advantages

of using the concept of cascade reactions in the synthesis of

different multifunctional poly(meth)acrylates. The synth-

eses of functional acrylate and methacrylate monomers

and their polymerization leading to multifunctional and

reactive poly(meth)acrylates will be discussed. Transacyla-

tion of MA and MMA as a substrate with different

functional alcohols in the presence of Novozyme 435 leads

to a mixture of functional monomers which subsequently

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are ‘‘in situ’’ copolymerized—after removal of Novozyme

435 by filtration—via free radical polymerization or

nitroxide mediated polymerization, resulting in poly-

(meth)acrylates with predefined functionalities designed

for a wide range of applications. Depending on the

application, the excess of M(M)A is removed by evaporation

and, or another functional monomer like HE(M)A is added to

the monomer mixture, which later is converted into a

reactive repeating unit with phenyl chloroformate obtain-

ing a functional and reactive copolymer suitable for further

polymer analogous reactions with primary amines.[93–95]

Chemoenzymatic Synthesis of(Meth)acrylates and Poly(meth)acrylates

The synthesis of highly functional and reactive poly-

(meth)acrylates via a chemical route is very demanding and

requires highly pure starting materials as well as inhibitors

in order to prevent the undesired polymerization. It was our

goal to develop a straightforward, mild, and rapid way for

the preparation of functional and reactive poly(meth)acry-

lates. The concept of our work is illustrated in Figure 2.

Starting with a technical monomer MMA or MA and a

H,CH3

OO + HO

H2C X

Enzymatictransacylation

H,CH3

OO

X

O

H,CH3

OO

H,CH3

OO

OH

OH

O

OHHO

O

HO

Free radicalpolymerization

Nitroxide mediatedpolymerization

Thermorespons

G(M)A

NP

DHH(M)A 2H

Figure 2. Schematic representation of the synthesis of functional an



functional alcohol, diol, or triol in an enzymatically

catalyzed step which is a transacylation catalyzed by

Novozyme 435, a mixture of monomers is obtained at

equilibrium. After the removal of Novozyme by filtration

the mixture of monomers can be polymerized via free

radical polymerization or CRP. As a CRP we have chosen

nitroxide mediated polymerization due to the polarity of

the hydroxy acrylates which were copolymerized for the

synthesis of novel poly(hydroxy acrylates)s. In some cases,

excess of MMA or MA was removed prior to polymerization

and another functional monomer, HE(M)A was added to the

mixture. The copolymers thus obtain are subjected to a

polymer analogous reactions using phenyl chloroformate

in order to prepare highly reactive poly(meth)acrylates

bearing phenyl carbonate groups which are known to react

fast and without side reaction with nucleophiles like for

example amines.

Enzymatic Synthesis of Functional (Meth)acrylates

In order to prepare functional acrylates or methacrylates

we investigated the transacylation of MA and MMA as

substrates and different functional monoalcohols as

reagents with Novozyme 435 as catalyst. Under certain

O

X

H,CH3

OO

H,CH3

OO

H,CH3

OO

N

O

O

H,CH3

O

OH

H,CH3

O

Bacteriostatic polymers

H,CH3

OO

N

Peptide/Protein-Polymer Conjugates

H,CH3

OO

O

O

O

ive polymers

G(M)A

PCE(M)A

P(M)A

DEGE(M)A D(M)A

DMAP(M)A

d reactive polymethacrylates via a cascade reaction.

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conditions this transacylation occurs with the result of a

mixture of two (meth)acrylates and two alcohols: the

starting materials, the functional (meth)acrylate, and the

methanol formed. It is worth mentioning that all transa-

cylation reactions were performed in bulk and no side

reactions occurred.[96]

All functional mono-alcohols used—dodecanol (D-ol), 3-

dimethylamino-1-propanol (DMAP), diethylene glycol

monomethyl ether (DEGME), and diethylene glycol ethyl

ether (DEGEE)—were successfully transacylated both, with

MA and MMA.

When two different alcohols were used simultaneously

for the transacylation reaction of the same substrate, the

following molar ratio of the components was chosen:

M(M)A/R1OH/R2OH¼ 1:0.5:0.5.

Optimization of the Transacylation of MethylAcrylate (MA) and Methyl Methacrylate (MMA) withFunctional Alcohols

In order to optimize the enzyme-catalyzed transacylation

reactions, the influence of different parameters on the

conversion of M(M)A was studied: (i) the influence of the

weight ratio substrate/enzyme, (ii) the conversion as a

fuction of time (time necessary to reach the equilibrium),

(iii) the influence of temperature, and (iv) the influence of

the molar ratio substrate/alcohol.

(i) T

www

he first remark with respect to the influence of the

enzyme concentration is the following: in the absence

of the enzyme no conversion or a conversion as low as

2 mol-% for DMAPMA and 5 mol-% for DMAPA is

observed. With increasing concentration of Novozyme

435 (1, 5, and 10 wt.-% with respect to M(M)A) the

reaction rate increases. For all enzyme concentrations

the conversion of MA is higher than that of MMA. One

reason for this result might be the higher sterical

demand of MMA as compared to MA in the enzymatic

transacylation reaction. In addition, MMA is a less

efficient acyl donor than MA.[97,98]

(ii) S
tudying the time necessary to reach the equilibrium
the same result—acrylates react faster than metha-

crylates—was obtained. The nature of the alcohol

used defines the reaction rate. The highest product

concentrations are found for D-ol: at equilibrium

49 mol-% DA is formed while DMA did not reach the

equilibrium: 36.5 mol-% after 144 h and 42 mol-% after

264 h. For both DMAP esters a concentration of 46 mol-%

is reached, however, at different times (for DMAPA

within 24 h, for DMAPMA within 96 h). The DEGME

and DEGEE esters result in the lowest concentration

with 34 mol-%.

(iii) T
he effect of temperature on the transacylation of
M(M)A was also studied for a molar ratio of M(M)A/

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functional alcohol 1:1 in bulk with an enzyme

concentration of 10 wt.-% with respect to M(M)A at

r.t. and at 70 8C. Under the conditions applied higher

conversion of the products are achieved at 70 8C than

at r.t. after 24 h. For acrylates the differences in

conversion are small and therefore the reaction at r.t.

should be preferred because of the milder reaction

conditions. For methacrylates a higher temperature is

needed to obtain an acceptable conversion within

24 h.

(iv) F
inally the influence of the molar ratio M(M)A/alcohol
on the transacylation efficiency at 70 8C and 24 h in

bulk with 10 wt.-% concentration of Novozyme 435

with respect to M(M)A was studied by decreasing the

ratio M(M)A/functional alcohol from 1:1 to 1:5 in

order to shift the equilibrium toward product forma-

tion. For the reaction of D-ol with MMA, an increase of

the alcohol concentration leads to a slight decrease of

DMA from 35 to 28 mol-%. For DMAP, an increase of

the alcohol concentration has no significant effect on

the conversion of MMA (33 mol-% vs. 30 mol-%). The

most significant change in the efficiency of the

transacylation by increasing the concentration of

the alcohol is found in reaction of MMA with DEGME.

When DEGME is used in an equimolar ratio with

respect to the substrate, 30 mol-% of DEGMMA are

formed, while, when a fivefold excess of DEGME is

used only 10 mol-% DEGMMA are obtained. An

explanation for these results might the inhibition

effect of the alcohol on the lipase. In the case of MA

as the substrate, with increasing alcohol concentra-

tion the absolute conversion of MA increases except

in the case of DEGME supporting our theory that

the DEGMEE inhibits the enzyme. In enzymatic

transacylation, the highest conversions are observed

for D-ol while the lowest are observed for DEGME.

Using an equimolar ratio the following conversions

were achieved: 45 mol-% DA, 40 mol-% DMAPA,

and 35 mol-% DEGMA, while using a molar

ratio substrate/alcohol of 1:5 the conversions were

76 mol-% for DA, 43 mol-% for DMAPA, and 30 mol-%

for DEGMA.

These results suggest that for an enzymatic transacyla-

tion the increase of the concentration of one component

does not have the expected result due to the fact that the

reaction medium is changed and consequently the enzyme

activity is changed. Based on these results we concluded

that the optimum conditions for the enzyme catalyzed

transacylation of M(M)A with different functional mono-

alcohols are: M(M)A/ROH¼ 1:1 mole/mole; t¼ 24 h;

T¼ 70 8C and an enzyme concentration of 10 wt.-% with

respect to M(M)A.

1, 32, 559–572

o. KGaA, Weinheim565

Table 1. Enzymatic transacylation of M(M)A with functional alco-hols (R–OH): molar composition of (M(M)A) and R(M)A.a)

M(M)A R(M)A

mol-% mol-%

MMA (86) DMA (14)

MA (55) DA (45)

MMA (73) DMAPMA (27)

MA (56) DMAPA (44)

MMA (79) DEGMMA (21)

MA (69) DEGMA (31)

MMA (81.5) DEGEMA (18.5)

MA (70) DEGEA (30)

a)All reactions were performed at r.t. for 24 h using 10 wt.-%

Novozyme 435 with respect to M(M)A. All the concentrations

were determined using 1H NMR spectroscopy.

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The molar ratios of the functional monomers obtained

R(M)A and M(M)A are summarized in Table 1.

Enzymatic Synthesis of Hydroxyl Functional(Meth)acrylates

This approach for the preparation of functional acrylate

monomers was expanded to the more demanding synth-

eses of hydroxy functional acrylates and methacrylates via

an enzymatic transacylation of MA and MMA with

different diols and triols.[99,100] In this way, mono- and

dihydroxy functional (meth)acrylate monomers were

obtained which are difficult to synthesize via conventional

methods and are difficult to purify and stabilize. To

investigate the effect of the alcohol structure used as

substrate on the formation of hydroxy functional mono(-

meth)acrylate monomers, symmetrical diols (ethylene

glycol; 1,3-propane diol; 1,4-butane diol; 1,5-pentane diol;

1,6-hexane diol), substituted symmetrical diols (2-methyl-

1,3-propane diol; neopentyl glycol), an asymmetrical diol

(1,2-propane diol), a symmetrical triol (glycerol) as well as

an asymmetrical triol (1,2,6-hexane triol) were selected.

Since the enzymatic transacylation is reversible mono-, di-,

and tri-functional (meth)acrylates can be obtained. None-

theless, sterical hindrance at the active site of the enzyme is

expected to suppress multiple acylation as well as acylation

of secondary alcohol groups. In addition the enantio-

selectivity during transacylation of the asymmetrical

racemic diol (1,2-propane diol) and triol (1,2,6-hexane triol)

was determined. Furthermore, it should be noted that the

reaction rate and product distribution depend on the

alcohol/M(M)A ratio,[43–45] the specificity of Novozyme 435

and the water activity.[101]



To obtain a better understanding of the mechanism of

the lipase-catalyzed transacylation we conducted kinetic

studies using 1,3Pdiol, 1,4Bdiol, 1,2Pdiol as well as glycerol

and MA and MMA as acyl donors. These alcohols were used

in order to synthesize hydroxy functional acrylates and

methacrylates that may be suitable for a wide variety of

applications.[31,38–40,102,103] 2-Methyl-2-butanol was used

as the solvent because of its polarity allowing the

dissolution of the alcohols while the enzyme retains its

catalytically active conformation.[104,105] The reaction

temperature was set to 50 8C, which is within the optimum

temperature range for the enzyme stability.[106] In order to

decrease the formation of bis(meth)acrylates, the molar

ratio acyl donor/alcohol was set to 1/number of OH groups

in the alcohol according to a theoretical model presented in

the literature.[43–45] The results show that acrylates react

faster than methacrylates. Further, the final conversions of

glycerol and 1,2Pdiol are lower than those of 1,3Pdiol and

1,4Bdiol which is explained by the higher polarity of the

reaction medium, by the higher sterical demand of these

substrates, and by the increase in viscosity of the medium

which makes diffusion to the active center of the lipase

difficult.[107] To these arguments, the lower reactivity of

secondary alcohol groups in glycerol and 1,2Pdiol should be

added. As a consequence, the unsubstituted a,v-diols

(1,3Pdiol and 1,4Bdiol) reach higher conversions than

a-substituted diols (glycerol and 1,2Pdiol).

Selectivity in Transacylation of Diols

The effect of the structure of the diols on the enzymatic

transacylation was also studied. For all cases except

1,3Pdiol, the final conversion of MA is higher than that of

MMA being in the range of 59–78 and 50–73 mol-%,

respectively. The conversion of both esters with EG is a

special case due to the hydrophilicity of EG, which may trap

the tightly-bound water necessary for retaining the tertiary

structure of the enzyme and thereby causing a rapid

deactivation of the lipase with the consequence of low

conversion.[101]

In the case of symmetrical diols (1,3Pdiol, 1,4Bdiol,

1,5Pdiol, and 1,6Hdiol) the product distribution mostly

follows the statistical rule as described in literature[43,44] for

chemical transacylation reactions, i.e., the enzyme does not

have any selectivity for the formation of mono(meth)acry-

late over bis(meth)acrylates. Nonetheless, in the case of the

reaction between MA or MMA and 1,3Pdiol the concentra-

tion of monosubstituted product is slightly higher than in

the case of 1,4 Bdiol, 1,5 Pdiol, and 1,6 Hdiol and also higher

than expected for the statistical product distribution. This is

most likely due to the chain length of the diol; the

monosubstituted product formed in the reaction with 1,3

Pdiol is more sterically hindered than longer diols. As a

result the formation of the disubstituted compounds is

suppressed. As expected, this effect is slightly stronger in

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the reaction with MMA. The effect of steric hindrance was

further evaluated by the use of substituted symmetrical

diols 2 Me1,3 Pdiol and NPG. Not surprisingly the highest

concentration of mono(meth)acrylates and the lowest of

bis(meth)acrylates were obtained with these diols. Again

the sterical hindrance of the monosubstituted compound

which could react with the acyl donor to result bis(meth)a-

crylates plays an important role. Iglesias et al.[43,44] found

that 73� 3 mol-% monoacrylate and 80 mol-% mono-

methacrylate are formed in the reaction of NPG and acid

chloride with a molar ratio NPG/acid chloride of 7:3, while

the calculated statistical amount of mono(meth)acrylate is

88 mol-%. Comparing these results with results obtained by

enzymatic transacylation having a similar molar ratio NPG/

M(M)A of 2:1, one can notice that higher amounts of the

monosubstituted (meth)acrylates (95 mol-% for the acry-

late and 92 mol-% for the methacrylate) are formed proving

the advantage of using Novozyme 435. One more important

observation was made when evaluating the product ratio

with time. In fact, the conversion of monoacrylate

formed in this reaction increases from 39 mol-% (t¼ 24 h)

to 56 mol-% (t¼ 120 h) with respect to the acyl donor MA,

while the concentration of bisacrylate remains constant at

3 mol-% up to 120 h. The same behavior was observed for

2Me1,3Pdiol where the concentration of the monoacrylate

increases from 60 to 67 mol-% and the concentration of

bisacrylates remained constant. This result is a conse-

quence of the sterical hindrance of the monoacrylates

which can not further react with the MA to form the

bisacrylates. A possible explanation for the higher con-

centration of 2-methyl hydroxypropyl acrylate (2MHPA)

than of 3-hydroxy neopentyl acrylate (HNPGA) is again

attributed to the sterical hindrance, NPG is more severely

sterically hindered than 2Me1,3Pdiol due to the second

methyl group in C2 position. Moreover, the higher sterical

demand of the transition state in enzymatic transacylation

leads to the formation of lower amounts of disubstituted

products in enzymatic transacylation than in chemical

transacylation.

When 1,2Pdiol, an asymmetrical diol comprising both a

primary and a secondary hydroxyl group, was used a very

small amount of bisacrylates (2 mol-%) was observed while

the formation of bismethacrylates was not detected at all.

This suppression of bis(meth)acrylate formation is due to

the lower reactivity of the secondary hydroxy group as well

as the increased sterical hindrance caused by the vicinity of

the two hydroxyl groups. However, the molar ratio of

monosubstituted (meth)acrylates is 4:1 (77:21 and 80:20)

which is similar to the ratio observed for the chemical

synthesis of 2-hydroxypropyl acrylate from propylene

oxide and acrylic acid where 25 mol-% of the minor isomer

(2-hydroxy isopropylacrylate, 2HIPA) is formed.[42,108]

Nonetheless, the chemical route is more demanding and

requires high purity reagents, CuCl as inhibitor, pyridine as




solvent as well as high temperature[108] in comparison to

the enzymatic catalyzed reaction.

Being a racemic diol the stereoselectivity of the lipase

was also determined. It was found that both enantiomers

reacted at the primary hydroxyl group to give 37 mol-% of

one isomer and 34 mol-% of its enantiomer. In contrast to

this result, it was previously reported for benzyl alcohol

derivatives that Novozyme 435 discriminates between

R and S enantiomers, since the enantioselectivity of

Novozyme 435 is very high for the secondary benzylic

alcohols but much less for the aliphatic alcohols.[109,110] In

addition, this difference might be an effect of the substrate

and the polarity of the solvent used (2Me2BuOH) which

apparently suppresses the selectivity of Novozyme 435. In

addition, the system may contain traces of water which also

has an effect on the enantioselectivity ofC. antarctica lipase

B (CAL-B) catalyzed reactions, since water might

be simultaneously a competitive and enantioselective

inhibitor and a competitive substrate.[111,112]

Selectivity in Transacylation of Triols

In the case of glycerol, a symmetrical triol, two equivalent

primary hydroxyl groups and a secondary hydroxyl group

of lower reactivity are involved in the reaction with the

acyl donor. Garcia et al. studied the direct synthesis of

monomers derived from glycerol and unsaturated acid

chlorides in a stoichiometrical ratio obtaining five products:

two mono-, two di-, and one trisubstituted monomer.[45]

Using Novozyme 435, and a molar ratio (meth)acrylate/

glycerol of 1:3 only two mono(meth)acrylates are formed

and traces of bis(meth)acrylates. The major product

obtained is the 1-glyceryl (meth)acrylate in a concentration

of 92 mol-% (for GMA) and 94 mol-% (for GA) after 120 h

whereas 2-glyceryl (meth)acrylate is obtained to a low

extent [1,3-dihydroxyisopropyl acrylate (DHIPA) with a

molar concentration of 3 mol-% and 1,3-dihydroxyisopro-

pyl methacrylate (DHIPMA) with 6 mol-%]. Only minor

amounts of bis(meth)acrylates (to a maximum 3 mol-%) are

formed. The different isomers of bis(meth)acrylates were

not determined.

Transacylation of MA and MMA with 1,2,6Htriol using

Novozyme 435 as catalyst was performed in 2Me2BuOH at

50 8C with a molar ratio MA/1,2,6Htriol of 1:3. Five products

were identified: three monosubstituted and two disubsti-

tuted hexanetriol derivates. Since the OH group in position

6 is the least hindered, 6-methacryloyl-1,2,6-hexanetriol

was found to be the major product (71 mol-%) followed by 1-

methacryloyl-1,2,6-hexantriol (19 mol-%) and 2-methacry-

loyl-1,2,6-hexanetriol (5 mol-%). The two bismethacrylates

identified were assigned to 1,6-dimethacryloyl-1,2,6-hex-

anetriol (4 mol-%) and 2,6-dimethacryloyl-1,2,6-hexanetriol

(1 mol-%) again based on the reactivity hypothesis. It was

assumed that 1,2-dimethacryloyl-1,2,6-hexanetriol is not

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formed due to sterical hindrance. The same assumption was

made for MA as acyl donor. The following distribution

of products was found: 86 mol-% of the two major products

(6-acryloyl-1,2,6-hexanetriol and 1-acryloyl-1,2,6-hexane-

triol), 8 mol-% of 2-acryloyl-1,2,6-hexanetriol, 4 mol-% of

1,6-diacryloyl-1,2,6-hexanetriol, and 2 mol-% of 2,6-diacry-

loyl-1,2,6-hexanetriol.[100]

The concentrations of mono-(meth)acrylates obtained

after enzymatic transacylation are presented in the Table 2.

Polymerization of the Monomer Mixture Obtained byTransacylation

Free Radical Polymerization

For the synthesis of multifunctional polymers the concept

of cascade reactions was applied: starting with M(M)A and

a functional alcohol ROH, in the first step transacylation

was performed with the result of a mixture of two

monomers (M(M)A and R(M)A), which in the second step,

after removal of the enzyme by means of filtration and of

M(M)A by distillation and, in some cases, after addition of 2-

hydroxyethyl (meth)acrylate (HE(M)A—was subjected to

free radical polymerization. Thus, for example after

transacylation reaction between MMA and D-ol, the

mixture was cooled to room temperature, Novozyme 435

was filtered off and AIBN, as a free radical initiator was

added. After polymerization, the polymer remained soluble

in the reaction medium and was isolated by precipitation in

methanol. A polymer with Mn ¼ 47 000 and Mw=Mn ¼ 2.3

was obtained. Moreover, the composition of repeating units

in the copolymer corresponds to the composition of

monomers in the feed proving the formation of a random

copolymer.

Table 2. Enzymatic transacylation of M(M)A with diols and triols: co

Mono-methacrylateb) Concentrationc)

mol-%

HEMA 0

3HPMA 38.1

4HBMA 26.5

5HPMA 31.6

2HPMA 18.6

2M3HPMA 29

3HNPGMA 18

GMA 31.5

1,2DHHMA 71d)

a)All reactions were performed in 2Me2BuOH at T¼50 8C for t¼ 24 h u

major isomer resulting from the enzymatic transacylation; c)The conce

concentration was determined after 120 h.



Several polymerization reactions were performed in

bulk, in butyl acetate, and ethanol. In order to prepare more

complex copolymers two distinct transacylation reactions

with two different alcohols were performed. In one case,

dodecanol was used as the alcohol, in the other case,

DMAPA. The two reaction mixtures were combined in a

certain ratio and then polymerized in bulk using AIBN as the

radical initiator. SEC analysis performed in DMAc revealed

the formation of the polymer with Mn ¼ 11 500 and

Mw=Mn ¼ 2. In order to introduce a reactive group into

the copolymer beside the functional groups a transacyla-

tion reaction with two different alcohols, DMAPA and D-ol

was performed and in the second step, after removal of the

enzyme by filtration, HEMA was added to the mixture of

monomers and copolymerized in ethanol at 90 8C for 9 h,

using AIBN as the free radical initiator. Thus, a copolymer

bearing hydrophobic, tertiary amino, and reactive groups

was obtained. Furthermore, a higher degree of hydrophi-

licity was achieved by introducing into the copolymer

beside the hydrophilic acrylate DEGMA resulting from the

enzymatic step, HEA in a mixture of molar ratio 1:1. A

functional and reactive copolymer soluble in water was

obtained.

Free radical polymerization of 3HPA and 4HBA did not

lead to soluble poly(hydroxyl acrylate)s, but a gel was

formed after 15–20 min. The gel formation can be explained

by the high concentration of bisacrylates, namely 10 mol-%

in 3HPA and 12 mol-% in 4HBA, leading to crosslinking

reactions. However, the free radical polymerization of

2Me3HPA that contains 7 mol-% bisacrylates yielded

soluble poly(2Me3HPA), the size exclusion chromatography

of the isolated polymer, however, revealed a trimodal

distribution with a number average molecular weight Mn

of 21 500 and a polydispersity index of Mw=Mn ¼ 9

ncentration of mono-(meth)acrylates at equilibrium.a)

Mono-acrylateb) Concentrationc)

mol-%

HEA 7.1

3HPA 63.5

4HBA 63.3

5HPA 64.1

2HPA 42.9

2M3HPA 59.8

3HNPGA 39

GA 50.7

1,2DHHA 72c)

sing 10 wt.-% Novozyme 435 with respect to M(M)A; b)Refers to the

ntration was determined by means of 1H NMR spectroscopy; d)The

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Table 3. Free radical polymerization of hydroxy acrylates obtainedvia enzymatic transacylation.

Monomera) Free radical polymerization

Xpb) (%) Mn

c) PDIc)

3HPA n.d.d) n.d.d) n.d.d)

4HBA n.d.d) n.d.d) n.d.d)

2Me3HPA 97 21 500 9

NPGA 86 17 600 2.3

GA 96 5 100 2

2HPA 98 14 000 2.3

DHHA 98 6 100 1.3

a)Major isomer in the feed; b)Total monomer conversion calculated

from 1H NMR spectroscopy; c)Number average molecular weight

(Mn) and polydispersity index (PDI) of purified polymers deter-

mined by size exclusion chromatography (SEC) using N,N-

dimethylformamide as eluent. GA, was measured in water;d)Not determined due to gelation.


www.mrc-journal.de

suggesting the formation of coupled chains induced by the

bisacrylates.

In contrast to 3HPA, 4HBA, and 2Me3HPA, all other

hydroxy acrylates showed the expected free radical

polymerization behavior resulting in monomodal molecu-

lar weight distributions with polydispersity indices around

2 as can be seen from Table 3. These results indicate that up

to 6 mol-% bisacrylate may be present in the monomer for

the preparation of soluble poly(hydroxyl acrylate)s with a

monomodal molecular weight distribution. Nonetheless,

the resulting soluble poly(hydroxy acrylate)s will still

contain unreacted acrylate units in the side chains and,

thus, might be used as reactive intermediates for cross-

linking or further functionalization.

It was reported in the literature that P(DEGEA) exhibits a

cloud point at �9 8C for a concentration of 0.1 wt.-%.[113] To

increase the cloud point of the polymer, copolymerization

with a more hydrophilic monomer is required. Thus, DEGEA

was copolymerized with HEA in different molar ratios: 25,

50, and 75 mol-%, under the same conditions. According to

the same procedure P(2HPA) and P(DHHA) were prepared

starting with the stock solutions obtained after enzymatic

transacylation. Finally, in order to increase the hydro-

phobicity of P(DHHA) direct copolymerization of the MA–

DHHA monomer mixture resulting after the enzymatic

transacylation reaction was performed.

Nitroxide Mediated Polymerization

The nitroxide-mediated polymerization of the new

hydroxy functional acrylates was investigated using




the optimized conditions: 110 8C polymerization tempera-

ture and 10 mol-% excess SG-1 free nitroxide relative to the

Blocbuilder alkoxyamine initiator.[114,115] Since the acrylate

monomers have a high propagation rate constant, excess of

free nitroxide is required to reduce the polymerization rate

and retain control over the polymerization. Since

the monomer solutions are viscous due to the presence

of diol/triol that was used in excess during the monomer

synthesis, a certain amount of DMF, which is known to

increase the polymerization rate in NMP,[116] was added to

decrease the viscosity and to prevent the loss of control

over the polymerization due to limited diffusion.

The NMP of the hydroxy acrylates obtained by enzymatic

transacylation was studied taking into account the amount

of bisacrylate present in the monomers. Kinetic investiga-

tions of 3HPA (10 mol-% bisacrylate) and 4HBA (12 mol-%

bisacrylate) revealed controlled polymerizations up to a

monomer conversions of 40%, after which the control is lost

due to coupling reactions caused by the presence of

bisacrylates. In the case of 5,6DHHA (6 mol-% bisacrylate)

and 2Me3HPA (7 mol-% bisacrylate), a controlled NMP was

achieved up to 50% monomer conversion while in the

case of NPGA (containing 5 mol-% bisacrylate) and GA

(containing 3 mol-% bisacrylate) the first order kinetic plots

remained linear up to high conversions. Moreover, for these

two latter monomers, the polymerization rate increased by

a factor of three when the monomer concentration was

doubled which is ascribed to the accelerating hydrogen

bonding effect which was suppressed at lower concentra-

tions in DMF.

The copolymerization kinetics of DEGEA with 25, 50, and

75 mol-% HEA were investigated, too. It was demonstrated

that the monomer composition does not influence the

control over the polymerization. The apparent rate constant

increased by a factor 1.5 for each 25 mol-% of HEA added. An

explanation for this experimental result might be the

interaction of the hydroxyl groups with the nitroxide via

hydrogen bonding which was found to accelerate the

NMP.[117] This effect is more pronounced for the copoly-

merization compared to the HEA homopolymerization due

to the higher monomer concentration. The incorporated

HEA fraction (FHEA) was found to be close to the HEA fraction

in the feed ( fHEA) for all the copolymerizations indicating a

nearly ideal copolymerization of the two monomers.

The copolymerization kinetics of monomer stock

solutions resulting from three enzymatic transacylation

reaction of MA with 1,2,6Htriol performed at the same

reaction conditions but for different times (2, 4, and 8 h)

were investigated and a first conclusion after analyzing the

purified copolymers by 1H NMR spectroscopy is that the

DHHA has a higher reactivity than MA which agrees with

the acceleration of the polymerization rates in NMP due to

hydrogen bonding formed between the monomers and the

initiator.

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Polymer Modification

Via cascade reaction we obtained multifunctional polymers

with hydrophobic, hydrophilic, tertiary amine, and

hydroxy groups. The hydroxy groups are eligible for

esterification with phenyl chloroformate and the tertiary

amine groups for quaternization.

The conversion of HEMA repeating units into PCEMA

repeating units results in highly reactive repeating units;

with primary amines additional functionality can be

introduced. The functional tertiary amino groups

(DMAP(M)A) were quaternized with iodomethane in

methanol solution at room temperature to obtain a

multifunctional cationic polymer with a preferred adsorp-

tion ability to negatively charged surfaces. By these

procedures amphipathic polymers were prepared.[116]

Applications

The multifunctional polyacrylates can be used for

surface coating. The concentration of ionic groups will

determine the strength of adhesion to the surface. Due to

the cooperativity of these effects a good adhesion is

expected. Depending on the ratio of hydrophilic to

hydrophobic groups and the environment, switchable

surfaces may be generated.

In addition, polymers containing hydrophobic and

quaternary ammonium groups are known to have anti-

microbial properties.[118]

Polymers that undergo phase transitions in response to

external stimuli are of great interest. The LCST is the critical

temperature below which a mixture is miscible in all

proportion. This behavior is based on hydrogen bonding

between water molecules and groups of the polymer chain.

The polymers with LCST behavior show a sudden and

mostly reversible change from hydrophilic to hydrophobic

that makes them attractive for application in biotechnol-

ogy, drug delivery systems,[31] tissue engineering,[32] and

biomolecule separation[33,34] but are also of interest for

catalysis.[35] The poly(hydroxy acrylate)s synthesized both

by FRP and NMP following the cascade reaction were

analyzed also for the thermo response in aqueous media. All

observed phase transitions were fully reversible and almost

no hysteresis was observed for the copolymers of DEGEA

and HEA as well as for the homopolymer P(2HPA),

nonetheless, in the case of the copolymers of DHHA and

MA during the cooling process, the rehydration of the

polymer chains seems to be hindered by hydrophobic

interchain interactions, leading to a marked hysteresis.

The hydroxyl groups of HEMA, copolymerized with the

monomer mixture resulting from the enzymatic transacy-

lation, were later converted with phenyl chloroformate into

the reactive phenyl carbonate or para-nitro phenyl

carbonate repeating units. An interesting application of



these multifunctional and reactive polymethacrylates is

their ability to react with different peptides/proteins. The

covalent binding of different proteins like silk peptide,

lysozyme, and CALB with the reactive groups attached to

the polymethacrylate back-bone was recently studied.[119]

Thus different bioconjugates were prepared. If in the case of

silk peptide and lysozyme a protein content of 20 and 24%

was determined, in the case of CALB no more than 11% of

protein was determined in the bioconjugate. The bioconju-

gates between CALB and different polymers showed

enzyme activity. An interesting approach for the formation

of peptide/protein-polymer bioconjugates was the use

of a miniemulsion for the reaction of the polymer with

peptides.

Conclusion

The transacylation of MA and MMA with alcohols, diols,

and triols is carried out under mild conditions, is easy and

rapid in processing and suitable for the preparation of

sensitive monomers. The resulting monomers are ready for

polymerization without further purification, thus, a wide

range of multifunctional and reactive poly(meth)acrylates

can be synthesized for different applications like bacterio-

static polymers, thermoresponsive polymers as well as

polymers suitable for the preparation of bioconjugates.

Received: November 17, 2010; Revised: December 22, 2010;Published online: January 31, 2011; DOI: 10.1002/marc.201000725

Keywords: enzymatic transacylation; free radical polymeriza-tion; hydrophilic polyacrylates; monomers; multifunctionalpolyacrylates; nitroxide mediated polymerization; surfaces

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